[PDF][PDF] SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein
T Inukai, A Inoue, H Kurosawa, K Goi, T Shinjyo… - Molecular cell, 1999 - cell.com
T Inukai, A Inoue, H Kurosawa, K Goi, T Shinjyo, K Ozawa, M Mao, T Inaba, AT Look
Molecular cell, 1999•cell.comAbstract The E2A-HLF fusion gene transforms human pro-B lymphocytes by interfering with
an early step in apoptotic signaling. In a search for E2A-HLF-responsive genes, we
identified a zinc finger transcription factor, SLUG, whose product belongs to the Snail family
of developmental regulatory proteins. Importantly, SLUG bears close homology to the CES-1
protein of C. elegans, which acts downstream of CES-2 in a neuron-specific cell death
pathway. Consistent with the postulated role of CES-1 as an antiapoptotic transcription …
an early step in apoptotic signaling. In a search for E2A-HLF-responsive genes, we
identified a zinc finger transcription factor, SLUG, whose product belongs to the Snail family
of developmental regulatory proteins. Importantly, SLUG bears close homology to the CES-1
protein of C. elegans, which acts downstream of CES-2 in a neuron-specific cell death
pathway. Consistent with the postulated role of CES-1 as an antiapoptotic transcription …
Abstract
The E2A-HLF fusion gene transforms human pro-B lymphocytes by interfering with an early step in apoptotic signaling. In a search for E2A-HLF-responsive genes, we identified a zinc finger transcription factor, SLUG, whose product belongs to the Snail family of developmental regulatory proteins. Importantly, SLUG bears close homology to the CES-1 protein of C. elegans, which acts downstream of CES-2 in a neuron-specific cell death pathway. Consistent with the postulated role of CES-1 as an antiapoptotic transcription factor, SLUG was nearly as active as Bcl-2 or Bcl-xL in promoting the survival of IL-3-dependent murine pro-B cells deprived of the cytokine. We conclude that SLUG is an evolutionarily conserved transcriptional repressor whose activation by E2A-HLF promotes the aberrant survival and eventual malignant transformation of mammalian pro-B cells otherwise slated for apoptotic death.
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